High‐Throughput Discovery of a Rhombohedral Twelve‐Connected Zirconium‐Based Metal‐Organic Framework with Ordered Terephthalate and Fumarate Linkers

Abstract We report a metal‐organic framework where an ordered array of two linkers with differing length and geometry connect [Zr6(OH)4O4]12+ clusters into a twelve‐connected fcu net that is rhombohedrally distorted from cubic symmetry. The ordered binding of equal numbers of terephthalate and fumarate ditopic carboxylate linkers at the trigonal antiprismatic Zr6 core creates close‐packed layers of fumarate‐connected clusters that are connected along the single remaining threefold axis by terephthalates. This well‐defined linker arrangement retains the three‐dimensional porosity of the Zr cluster‐based UiO family while creating two distinct windows within the channels that define two distinct guest diffusion paths. The ordered material is accessed by a restricted combination of composition and process parameters that were identified by high‐throughput synthesis.


Introduction
Metal-organic frameworks,M OFs,a re crystalline and porous materials composed of metal-based nodes and organic linkers. [1] They demonstrate extensive structural diversity and tunability due to the plethora of available choices for and arrangements of these building blocks. [2] Many key MOF structural families [3] arise from systematically expandable topologies that are defined by the chemistry and geometry of the interaction between as ingle node and as ingle linker. These topologies generate the structures for applications [4] that depend on the pore geometries and dimensionalities, arising from the number, nature and connectivity of windows, channels and cages in the materials.T he positionally ordered introduction of multiple linkers into the network topologies of these key families offers ad istinct mechanism for precise control of the guest-accessible space.T he associated requirement for extra linker components can be expected to complicate full exploration of the resulting larger chemical space.
Automated high-throughput (HT) methods for materials synthesis and analysis are powerful tools for the systematic exploration of multiparameter chemical systems. [5] They enable the screening of larger numbers of reactions than purely manual methods,a ccelerating the detailed investigation of complex chemical spaces.T he large numbers of variables associated with MOF synthesis and in particular with multiple linker MOFs renders HT synthesis an appropriate approach for the discovery of new phases. [6] Zirconium carboxylate MOFs built from the [Zr 6 O 4 -(OH) 4 ] 12+ cluster unit have received considerable attention not only for their high chemical stability but also for their three-dimensional porosity,s tructural diversity [7] and ability to incorporate many chemical functionalities. [8] The1 2-connected, 12-c, framework of UiO-66 [9] (Figure 1a)w ith facecentered cubic (fcu)t opology is based on an octahedral Zr 6 core whose 12 edges are bridged by ditopic carboxylate linkers to form the extended structure:t he four m 3 -O 2À and four m 3 -OH À ligands are located alternately above each triangular face of the core.T he positions of the twelve carboxylate linkers around the inorganic cluster define ac uboctahedron. UiO-66 has been the prototype for the development of several mixed-linker MOFs.Cubic structures of randomly distributed linkers with the same lengths are produced either by single-step synthetic protocols [10] or by postsynthetic linker exchange reactions. [11] Also the use of linkers with different lengths in single-step reactions affords disordered cubic structures. [12] Alternatively,materials where linkers of different lengths are ordered to decorate the framework in aw ell-defined manner have been synthesised by sequential installation of linkers. [13] This relies on the initial preparation of an 8-c framework with bcu topology where only eight of the twelve edges of the Zr 6 octahedron are bridged by linkers.Asubsequent synthetic step then introduces four linkers onto the remaining edges. [14] This narrows the synthetic space to afford ordered mixed-linker materials, but necessarily constrains the composition to a2:1 ratio of the first to the second linker.I ta lso restricts the accessible ordered two-linker structures,because the stepwise assembly gives the parent structure decisive influence on the outcome. Forexample,the porosity is always characterised by one type of window between the tetrahedral and octahedral cages. Reflecting these limits,there has been no report of an fcu Zr MOF with ordered multiple linkers obtained from as inglestep synthesis,o ro fa ny such material with al inker ratio distinct from 2:1o rastructural arrangement of linkers different from 8plus 4. Theaim of this study is single-step selfassembly of an ordered array of two linkers that is not subject to these constraints.
We present an ew 12-c Zr MOF with equal content of ordered terephthalate and fumarate linkers.This material was prepared in as ingle-step synthesis and discovered by highthroughput exploration of the chemical space defined by the reagents ZrOCl 2 /terephthalic acid/fumaric acid/formic acid in DMF.T he material is based on the underlying fcu topology where the [Zr 6 O 4 (OH) 4 ] 12+ clusters are connected by six terephthalate and six fumarate linkers.This ordered arrangement of the two distinct linkers produces trigonally distorted tetrahedral and octahedral cages which share two types of windows that are differentiated by the linkers that describe them. This is the first fcu Zr MOF with two windows and reflects the opportunity to control three-dimensional MOF porosity precisely through multiple linker chemistry.

Results and Discussion
Thed itopic linkers terephthalate and fumarate were selected for the exploration of mixed-linker Zr MOF synthesis as they both form 12-c fcu topology MOFs,UiO-66 and MOF-801 [15] (Figure S1), respectively,a nd they differ in length (the distance between carboxylate carbons is 6.0 and 3.9 ,r espectively) and shape (linear versus zig-zag, Figure 1c). These distinct linker geometries can confer structural diversity on the products.
Thes ynthesis of UiO-66 [16] and MOF-801 [17] has been achieved over ab road range of overall concentrations and compositions of the starting materials in various solvent systems.W echose ZrOCl 2 ·8 H 2 Oasthe metal source because it forms the stable solutions essential for automated dispensing. We then selected the reaction conditions to be explored for the robotic high-throughput synthesis of Zr-based MOF with mixed terephthalate (T) and fumarate (F) linkers by evaluating reported conditions from the literature where ZrOCl 2 ·8 H 2 Ow as used (summarised in Figure 2a nd Tables S5 and S6) in fcu MOF synthesis.The solvent, DMF,and modulator, formic acid (FA), were chosen to be the same for all reactions as they have been used extensively in synthesis of both UiO-66 and MOF-801. Thet ime and temperature of reaction were fixed at 48 hours and 120 8 8C, respectively,t o provide sufficient duration and high enough temperature to favour formation of an ew phase without encountering problems due to DMF volatility.I no rder to exploit the liquid-handling robot used to prepare reaction mixtures,w e selected conditions that enabled the use of stock solutions of the reaction components.T he implicit necessity for these solutions to be stable at room temperature throughout the duration of the automated sample preparation, which required up to 2hours to complete,i mposed al imit on the concentration of the ZrOCl 2 ·8 H 2 Os tock solution used of 0.0225 M, because of its solubility in DMF.The volume of this stock solution added to each reaction mixture was also fixed, giving each 10 mL-scale reaction mixture the same ZrOCl 2 ·8 H 2 Oc oncentration of 38 mg/10 mL. Thec ombinatorial parameters explored in the high-throughput syntheses were thus limited to the ratio between the two linkers,(T:F), and their total amount relative to the quantity of Zr, Zr:(T + F), as well as the amount of formic acid (FA:Zr). These three parameters were expected to have the largest influence on the chemistry and potential formation of anew phase. [18] We adopted agrid search and used automated dispensing of reaction mixtures by liquid-handling robots to accelerate the exploration of the space.T he chemical space was subdivided to span ab road range of compositions,c overed by aset of 45 points (Table S2)  was added to each of the reaction mixtures to give each vial the same fill factor,with atotal volume of reaction of 10 mL. All of the reaction mixtures were prepared in parallel, with the reaction components added with the same order of addition (formic acid-ZrOCl 2 -T:F stock-DMF), and were run under the same condition (120 8 8Cf or 48 hours).
After the completion of the reactions,t he samples were classified by visual inspection. Only 11 out of 45 (light grey in Figure 3a)yielded no solid product. PXRD showed that each of the 34 solid products is crystalline.T he patterns of the samples prepared with only one linker confirmed the presence of the known phases of UiO-66 for terephthalate and MOF-801 for fumarate ( Figures S3 and S7) under the HT reaction conditions used in this study.T he mixed-linker samples of the reaction sets displayed in red and purple in Figure 3a display diffraction peaks at low angle that correspond only to those of the cubic phases.T heir diffraction patterns were fitted to cubic unit cells with lattice parameters between the cubic end-members MOF-801 and UiO-66 ( Figures S4-S6 and S8). These samples can be characterised as single phase solid solution terephthalate/fumarate Zr MOFs similar to those reported recently by Zhou. [12] The presence of both linkers in these samples has been verified by 1 HNMR analysis on the digested solids ( Figures S9-S11), where the molar ratio T:Fi sh igher than the nominal value, for example asolid synthesised with T:F = 1:1contains T:F = 1:0.64 (Table S8).
TheP XRD pattern from the sample with composition Zr:T:F = 0.5:0.25:0.25 and FA :Zr = 334, marked as the circled blue point in Figure 3a,exhibits three sharp peaks that do not correspond to any of the known phases of the studied system and cannot be indexed with the cubic cell ( Figure 3b). The sample Zr:T:F = 0.25:0.375:0.375 and FA :Zr = 501, marked as the circled green point in Figure 3a,also presents the same peaks with much lower intensity ( Figure 3c). These two results were identified as hits,m ajor and minor,r espectively, in the search for anew phase in the present system and guided the continued exploration in as econd, focussed library that explored asmaller volume of the chemical space.
Thesecond iteration of reactions was focused in aregion of the chemical space ( Figure 4a)that was selected to include the two hits from the first batch and to have its centre closer to the major than the minor hit. This volume was fifteen times smaller (Supplementary Note 2a nd Figure S12 in the Supporting Information) than that described by the first set of samples,a nd was more densely covered with 54 reaction compositions.T he linker molar ratio,T :F,r anges from 0.375:0.625 to 0.625:0.375 because both hits were obtained from reaction mixtures with equimolar amounts of linkers. TheF A:Zr ratio ranged from 292 to 501, divided into six selected values.For each of these six FA :Zr ratios,the Zr:(T + F) molar ratio adopted three values (Table S4). Therest of the reaction conditions (use of DMF as solvent, temperature 120 8 8Cf or 48 hours,s ize of vials 20 mL and the execution protocol with the robot remained) exactly the same as in the first batch.
As observed in the first batch, in the second batch there were distinct regions where the reactions yielded no solid product, which were the mixtures with low linker and high modulator content, and regions where solid product was formed. PXRD patterns of the solid products (Figures 4a nd S13) showed that the target new phase was observed only in the samples prepared with an equimolar ratio of the two linkers (Figure 4b), while the rest of the samples displayed diffraction peaks that correspond to the solid solution phases (Figure 4c). This noticeable difference between samples prepared with T:F = 0.5:0.5 and T:F = 0.625:0.375 demonstrates the requirement for large number of experiments,  (Table S5), identified by blue symbols), and MOF-801 (5 reported conditions (Table S6), identified by yellow symbols) with ZrOCl 2 ·8 H 2 Oasthe metal source and formic acid (FA) as the modulator.T hese conditions, and the requirements of the liquid-handling robot for full solubility of reagents at room temperature, in contrast to literature studies that might use both solid and liquid reagents, were used to select the range of conditionse xplored for the synthesis of aZr-based MOF with mixed terephthalate and fumarate linkers. Conditions in which one would reasonably expect to obtain acrystalline product given the constraints of this specific chemistry on the robotic platform used are classed as "preferred" (indicated by the region highlighted in green), whilst those where the formation of acrystalline product within the accessible chemistry here is seen as less likely,a re classed as "considered" (indicated by the regions highlighted in purple). The regions outlined in red indicate the range over which each of these variables was explored in this work. The time and temperature used were fixed at 48 hours and 120 8 8Crespectively, as was the identity of the solvent, DMF, and modulator,formic acid. The amount of ZrOCl 2 ·8 H 2 Oused was limited by its solubility in DMF and fixed at 38 mg/10 mL.  facilitated by high-throughput methods,t oi solate the new phase even within the narrowed chemical space of the second batch, and emphasises the contrast in precision of conditions required to form this phase with the broad region over which the linker-disordered cubic phases form ( Figure S14). The sample with composition Zr:T:F = 0.5:0.25:0.25 and FA :Zr = 376 exhibits the pure form of the new phase.Z r 6 (BDC) 3 -(Fum) 3 crystallizes in R3 (space group no.1 48), a = b = 12.69646 (7) , c = 37.9733(4) , V = 5301.20(8) 3 .T he space group assignment was based on the observed systematic absences.S tructure solution was carried out using synchrotron PXRD data collected at beamline I11 (Diamond Light Source, l = 0.826596(10) )t hrough ac ombined Monte Carlo/Simulated Annealing approach with TOPA S-Academic V5, followed by Rietveld refinement (see Characterisation Te chniques and Figure S16). During refinement, the occupancies of the linkers were fixed at the values determined by 1 HNMR analysis of the activated material ( Figure S23), while the occupancies of MeOH molecules located in the pores were obtained from refinement.
Zr 6 (BDC) 3 (Fum) 3 is a12-c framework of [Zr 6 O 4 (OH) 4 ] 12+ clusters connected by six terephthalates and six fumarates in the fcu topology (Figure 5a). TheZ r 6 core of the cluster adopts trigonal antiprismatic geometry,w here the two equilateral triangular faces align with the unique threefold axis of the rhombohedral structure.T he edges of these equilateral triangular faces are occupied in an ordered manner only by the terephthalate linkers (Figures 5b and S17a), which connect with six other clusters,t hree in the close-packed layer above and three in the layer below (Figure 5d). The remaining six edges of the cluster are occupied by fumarates (Figures 5c and S17b) that connect to six other clusters in ahexagonal planar fashion-these are the neighbours within the close-packed layer occupied by the cluster itself (Figures 5d and S18). Thes ix remaining faces of the trigonal antiprism Zr 6 core are then isosceles triangles described by one terephthalate-bridged and two fumarate-bridged edges.
Thel ower rhombohedral symmetry of Zr 6 (BDC) 3 (Fum) 3 ( Figure 6a)compared to the cubic Fm3 m structure of UiO-66 ( Figure 6c)isassociated with this ordered arrangement of the two linkers.T he shorter length of fumarates compared to terephthalates shrink the intercluster distances in the ab plane in comparison with those that have a c axis component and induces the rhombohedral distortion (Figures 5d,6 ca nd S18). Thus,t he unit cell volume per formula unit of Zr 6 -(BDC) 3 (Fum) 3 ,1 767 3 ,l ies in between those of UiO-66 (2231 3 )a nd MOF-801 (1418 3 ). In contrast to MOF-801, where the zigzag shape of the fumarates causes the alternating tilting of the Zr clusters about the unit cell vectors (Figure 6d), the clusters of Zr 6 (BDC) 3 (Fum) 3 adopt the same orientations (Figure 6b), resulting in asymmetric binding of the fumarates to the Zr centres ( Figure S19), with Zr-O Fumarate bond lengths of 1.964(13) and 2.363(4) .T he terephthalates are essentially symmetric bridges,w ith Zr-O Te rephthalate bond lengths 2.148(2) and 2.079(4) .
Zr clusters and fumarates thus form close-packed hexagonal layers,d escribing the ab plane of the rhombohedral structure,w hich are connected by the terephthalates (Figure 7c)i nt he third dimension. This regular arrangement of two linkers with different lengths on the fcu net defines the unique shapes of the cages and windows,a nd controls the details of the three-dimensional pore system. Thetetrahedral cage adopts at rigonal pyramidal shape and the octahedral cage has at rigonal antiprismatic shape ( Figure S20 aa nd b). These distorted tetrahedral and octahedral cages are connected by two types of triangular windows,o ne fully composed of fumarates,3 F, (Figure 7a)a nd one composed of two terephthalates and one fumarate,2T1F, (Figure 7b). In contrast to the known Zr fcu MOF structures that all have one type of window,Z r 6 (BDC) 3 (Fum) 3 has two distinct types of window between the cages (Figure 7d). Thed egree of rhomdohedral distortion in Zr 6 (BDC) 3 (Fum) 3 is expressed in the different distances between opposing windows of the same type in the octahedral cage,measured through the cage centre.T his distance between 3F windows is 12.650 (2) and between 2T1F windows is 10.555(3) ( Figure S20 ca nd d). clusters (cyan, Oinr ed) connected by terephthalate (blue) and fumarate (orange) linkers. Yellow and purple spheres represent the centres of the distorted tetrahedral( trigonal pyramid) and octahedral (trigonal antiprism) cages, respectively.b)T erephthalate linkers (blue) occupy the edges of the two equilateral triangular faces of the Zr 6 trigonal antiprisms that are aligned with the threefold axis of the rhombohedral structure. The Zr-Zr distance defining these edges is 3.523(6) (c) Fumarate linkers (orange) occupy the remainings ix edges of the antiprism,w ith Zr-Zr distances of 3.460(3) ,which connect the equilateral triangular faces (only two of the linkers are shown for clarity in (b)). The terephthalate-bridged edges of the Zr 6 trigonal antiprism are rendered in adarker colour in (b) and (c). d) The distorted Zr 6 O 4 (OH) 4 (COO) 12 cuboctahedra defined by the ligand oxygen positions are arranged in fcc packing, where three closepacked layers in the ABC sequencea re shown, viewed perpendicular to the threefold axis. Each cuboctahedron is connected by the long blue edges (terephthalates) to six clusters in the layers above and below its layer,and by the short orange edges (fumarates) to six other clusters in the same layer.The close-packed fumarate-only layers that define the ab plane are stacked along the unique threefold axis of the rhombohedral cell.
Thetwo windows in Zr 6 (BDC) 3 (Fum) 3 define two types of possible diffusion pathways for guest molecules.I nt he path parallel to the Zr fumarate layers,t he guest passes through the 2T1F window only (blue arrow in Figure 7c), whereas in any path that involves motion out of this plane,t he guest passes through both windows (the blue-and-yellow arrow in Figure 7c). There is no diffusion pathway involving exclusively 3F windows.This can be easily demonstrated by the net representation (Figure 7d), where any pathway entering at etrahedral cavity through the 3F window (three yellow edges) will have to continue through one of the three 2T1F windows (two blue and one yellow edge).
Compositional and porous characterisation of Zr 6 (BDC) 3 -(Fum) 3 was performed on as ample prepared from synthesis that involves ZrCl 4 as starting material because this affords the product at higher yield, 83 %, than the ZrOCl 2 -based synthesis,1 5%.( Experimental protocols Supporting information). Thephase purity of this sample was confirmed with PXRD ( Figure S24). Theorganic components of Zr 6 (BDC) 3 -(Fum) 3 were analysed by 1 HNMR after digestion of the sample in NaOD/D 2 O. TheM eOH-exchanged sample displays molar ratios T:F:MeOH:FA = 1:0.92:3.4:0.2 (Fig-ure S22). Thed eviation from the equimolar composition between the two linkers and the presence of formates in this sample are indicative of missing linker defects in the Zr 6 -(BDC) 3 (Fum) 3 structure.I ti sw ell known that modulated synthesis of Zr MOFs promotes the formation of defects, [19] which are predominantly missing linkers and occasionally missing clusters. [20] It has been demonstrated that single crystals of UiO-66 contain 10 %o fm issing linkers, [16a, 20a] whereas powders of UiO-66 prepared with trifluoroacetate modulator contain 33 %o fm issing linkers. [21] Solvent exchange with MeOH produces pairs of MeO À /MeOH as terminal ligands on the defect sites of UiO-66. [22] To provide am ore accurate framework composition of Zr 6 (BDC) 3 -(Fum) 3 ,t he MeOH exchanged sample was activated under high vacuum at 60 8 8Ct or emove non-coordinating MeOH from the pores before digestion and 1 HNMR analysis ( Figure S23), while the structure of the material is preserved ( Figure S24 (b). This contrasts with their arrangement in MOF-801 (d), where the zig-zag shape of the fumarate linkers causes the clusters to tilt in alternating directions about the intercluster vectors that define the unit cell directions.E ach Zr in Zr 6 (BDC) 3 (Fum) 3 has adistorted square antiprismaticc oordination environment, as the oxygens from fumarate and terephthalateadopt different bond lengths to the Zr centre ( Figure S19). This is reflected in the distinction between the square faces defined by the ligand oxygens in (d), and the distortion of this square into two edge-sharing triangles in (b).
in the idealised composition, are missing, with their sites in each cluster occupied by formate and pairs of MeO À /MeOH ligands.T hese missing linkers have an effect on the porous properties of the material, as they generate extra accessible space and decrease the density of the framework. Zr 6 (BDC) 3 -(Fum) 3 exhibits at ype IN 2 adsorption desorption isotherm ( Figure 8) with aB ET surface area of 783 m 2 g À1 and ap ore volume of 0.32 cm 3 g À1 .B oth experimental values are larger than the theoretical values,7 14 m 2 g À1 and 0.26 cm 3 g À1 respectively calculated using Zeo ++ (see Supplementary Note 4i nt he Supporting Information). [23] Thee xperimental BET surface area and pore volume of Zr 6 (BDC) 3 (Fum) 3 lie between the respective values of MOF-801 (690 m 2 g À1 /0 .27 cm 3 g À1 )a nd UiO-66 (1290 m 2 g À1 / 0.49 cm 3 g À1 ).
[17a] Theo rdered arrangement of two ditopic linkers in the fcu net controls the global porous properties, surface area and pore volume,a sw ell as the local ones,t he size and the shape of the individual cages and windows.T his approach offers additional tuning capabilities for the porous properties of ahigh symmetry net through the precise locallyand long-range ordered definition of intermediate surface areas created from distinct pore shapes.T he well-established isoreticular expansion or contraction of as ingle linker MOF offer large changes in surface area and pore size that preserve the shape and number of cages and windows, [24] while solid solution mixed-linker MOFs generate intermediate surface areas in locally heterogeneous pore systems arising from longrange multiple linker disorder. [12] Conclusion Thechemical space defined by ZrOCl 2 ,terephthalic acid, fumaric acid and formic acid was explored to identify new MOF by high-throughput experimental screening.T he twolinker ordered MOF,Z r 6 (BDC) 3 (Fum) 3 ,w as the only new phase discovered and it is formed in an arrow region of this space,i nc ontrast to the linker-disordered cubic material formed by the same two linkers.T he identification of the linker-ordered system by single-step self-assembly then required the screening at fine compositional resolution that is enabled by the high-throughput approach. Although each linker individually affords an important, well-studied member of the key fcu net Zr-based MOF family,both with one pore window and asingle guest diffusion path, Zr 6 (BDC) 3 (Fum) 3 is not as imple intermediate between these structures.R ather, its structure is generated by ordered linker decoration of the fcu net that breaks the symmetry to introduce anisotropy into the three-dimensional porosity,which is now characterised by two distinct diffusion paths.The ordering of terephthalate and fumarate binding to the [Zr 6 O 4 (OH) 4 ] 12+ cluster creates two windows of different shape that describe the distorted octahedral and tetrahedral cages defining these paths.T his ordering precisely defines the porosity locally to each cage and is distinct from the locally heterogeneous tuning offered by disordered multiple linker MOF average structures.T he resulting simultaneous tuning of pore size and shape,w hich affords interval pore volume between the parents,d iffers from isoreticular expansion in that it tunes within ad efined range of extra-framework space.M ultiple linker ordered decoration of canonical single linker MOF topologies can harness the resulting combinatorial and chemical diversity of linker sets to generate new porous materials families where the size and shape of the internal space can be precisely modified for optimal guest interaction.

Associated Content
TheS upporting information file contains detailed experimental procedures and results from PXRD, 1 HNMR and TGA measurements.Italso contains additional figures,tables and notes.D eposition Numbers 2089846 contain the supplementary crystallographic data for this paper.T hese data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service www.ccdc.cam.ac.uk/ structures.T he datasets supporting the findings of this study are available from the University of Liverpool and can be found at https://datacat.liverpool.ac.uk/id/eprint/1460. Figure 8. N 2 adsorption desorption isotherm at 77 KofZ r 6 (BDC) 3 -(Fum) 3 ,which has aBET surface area of 783 m 2 g À1 and pore volume of 0.32 cm 3 g À1 .T he closed symbols correspond to the adsorption branch and the open symbols to the desorption branch.